New gene-editing technology partially restores vision in blind animals

February 25, 2017

shutterstock_353873630

Salk Institute researchers have discovered a holy grail of gene editing — the ability to, for the first time, insert DNA at a target location into the non-dividing cells that make up the majority of adult organs and tissues. The technique, which the team showed was able to partially restore visual responses in blind rodents, will open new avenues for basic research and a variety of treatments, such as for retinal, heart and neurological diseases.

“We are very excited by the technology we discovered because it’s something that could not be done before,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of the paper published on November 16, 2016 in Nature. “For the first time, we can enter into cells that do not divide and modify the DNA at will. The possible applications of this discovery are vast.”

Until now, techniques that modify DNA — such as the CRISPR-Cas9 system — have been most effective in dividing cells, such as those in skin or the gut, using the cells’ normal copying mechanisms. The new Salk technology is ten times more efficient than other methods at incorporating new DNA into cultures of dividing cells, making it a promising tool for both research and medicine. But, more importantly, the Salk technique represents the first time scientists have managed to insert a new gene into a precise DNA location in adult cells that no longer divide, such as those of the eye, brain, pancreas or heart, offering new possibilities for therapeutic applications in these cells.

To achieve this, the Salk researchers targeted a DNA-repair cellular pathway called NHEJ (for “non-homologous end-joining”), which repairs routine DNA breaks by rejoining the original strand ends. They paired this process with existing gene-editing technology to successfully place new DNA into a precise location in non-dividing cells.

“Using this NHEJ pathway to insert entirely new DNA is revolutionary for editing the genome in live adult organisms,” says Keiichiro Suzuki, a senior research associate in the Izpisua Belmonte lab and one of the paper’s lead authors. “No one has done this before.”

First, the Salk team worked on optimizing the NHEJ machinery for use with the CRISPR-Cas9 system, which allows DNA to be inserted at very precise locations within the genome. The team created a custom insertion package made up of a nucleic acid cocktail, which they call HITI, or homology-independent targeted integration. Then they used an inert virus to deliver HITI’s package of genetic instructions to neurons derived from human embryonic stem cells.

“That was the first indication that HITI might work in non-dividing cells,” says Jun Wu, staff scientist and co-lead author. With that feat under their belts, the team then successfully delivered the construct to the brains of adult mice. Finally, to explore the possibility of using HITI for gene-replacement therapy, the team tested the technique on a rat model for retinitis pigmentosa, an inherited retinal degeneration condition that causes blindness in humans. This time, the team used HITI to deliver to the eyes of 3-week-old rats a functional copy of Mertk, one of the genes that is damaged in retinitis pigmentosa. Analysis performed when the rats were 8 weeks old showed that the animals were able to respond to light, and passed several tests indicating healing in their retinal cells.

“We were able to improve the vision of these blind rats,” says co-lead author Reyna Hernandez-Benitez, a Salk research associate. “This early success suggests that this technology is very promising.”

The team’s next steps will be to improve the delivery efficiency of the HITI construct. As with all genome editing technologies, getting enough cells to incorporate the new DNA is a challenge. The beauty of HITI technology is that it is adaptable to any targeted genome engineering system, not just CRISPR-Cas9. Thus, as the safety and efficiency of these systems improve, so too will the usefulness of HITI.

“We now have a technology that allows us to modify the DNA of non-dividing cells, to fix broken genes in the brain, heart and liver,” says Izpisua Belmonte. “It allows us for the first time to be able to dream of curing diseases that we couldn’t before, which is exciting.”


Story Source:

Materials provided by Salk Institute. Note: Content may be edited for style and length.

Beyond ‘Back to the Future’: Experts Serve Up Tech Predictions for 2045

December 06, 2015

logo

Just How Much Did ‘Back to the Future’ Get Right about October 2015?2:19

In “Back to the Future Part II,” Marty McFly and Doc Brown travel from 1985 to October 21, 2015, to find a world filled with flying cars, hoverboards and self-drying jackets.

Those predictions didn’t exactly pan out, although people are working on each of those concepts. (Screenwriter Bob Gale did get a lot of things — from drones to fingerprint scanners — right, as he told TODAY earlier this year.)

The future is now, and it’s pretty cool. But what will the world be like in another 30 years? Three futurists shared their predictions with NBC News.

Katie Aquino, a.k.a. ‘Miss Metaverse’: Super-fast travel, nanomedicine and virtual immortality

“No longer will expensive and lengthy flights be the norm for world travel,” said the futurist and filmmaker known as Miss Metaverse. Instead, frictionless maglev trains will allow “us to travel at speeds in excess of 6,000 miles per hour while only feeling a G1 gravitational force, the same we feel when riding in a car.”

At those speeds, going from New York to Beijing will only take two hours. And if you get sick on your trip?

“Nanotechnology, although not a hot topic today, will likely unlock the keys to destroying cancer cells and ‘programming’ stem cells for a myriad of health benefits in the future,” she said.

Customized drugs will solve a lot of ailments. Death isn’t one of them, but we could still find a way to become immortal … kind of.

Related: 10 Ways to Celebrate ‘Back to the Future’ Day

“Our future lives may truly be limitless thanks to an organization known as the 2045 Initiative that’s working towards a goal of uploading human consciousness into synthetic avatars,” she said. “Much like in the movie ‘Avatar,’ humans may evolve into what are theoretically known as post-humans, human consciousness in upgraded or synthetic bodies.”

Jamais Cascio: Jurassic pets and augmented reality clothing

Love the movie “Jurassic Park” but don’t like being eaten by terrifying symbols of man’s hubris?

Synthetic biology could let people create “miniature versions of various dinosaurs or other prehistorical creatures,” said writer and futurist Jamais Cascio. That might include a “mini-Velociraptor on a leash, with the right behavior modification to make sure it’s safe to be around,” or a “micro-Brontosaurus that’s perfect for a kid to ride.”

Related: How ‘Jurassic World’ Created a Terrifying New Dinosaur

Of course, you want to look when riding around on your designer dinosaur. Hence the augmented reality clothing, which, Cascio said, will be visible to people wearing the “ubiquitous smart glasses, digital contact lenses, and eye upgrades.”

“Imagine a dress that looks like (and acts like) it’s made of water,” he said. “Or a Halloween costume that appears to be entirely made of living spiders.”

That would look great with a pair of sneakers with power laces.

Inventor sets new record for hover board flight0:22

James Canton: Digital memories and robot soldiers

Sharing a Facebook photo won’t seem very impressive in 2045, according to James Canton, a futurist, writer and business consultant.

That’s because people will share “entertainment memories,” which are “like real-time videos,” he said, “except others can experience the emotion, physical sensation and actual experience as if they were there.”

Intense and kind of creepy! Gene-editing will eliminate genetic diseases, he predicted, and replica organs will be printable on demand.

Genetic testing shows likelihood for some diseases1:40

And yes, “Terminator” fans, there will be machine combat as “robots fight our wars, no more human soldiers.”

There is no guarantee that any of these technologies will arrive, of course. Hopefully by 2045, we will see at least some of the predictions from “Back to the Future Part II” come true, although there is a decent chance we still won’t have flying cars and the Chicago Cubs (currently losing in the playoffs to the Mets) will still be waiting for their first World Series win since 1908.

http://www.nbcnews.com/tech/innovation/beyond-back-future-experts-serve-tech-predictions-2045-n447311

Beyond ‘Back to the Future’: Experts Serve Up Tech Predictions for 2045

November 8, 2015

Back-to-the-Future-Title-Card

In “Back to the Future Part II,” Marty McFly and Doc Brown travel from 1985 to October 21, 2015, to find a world filled with flying cars, hoverboards and self-drying jackets.

Those predictions didn’t exactly pan out, although people are working on each of those concepts. (Screenwriter Bob Gale did get a lot of things — from drones to fingerprint scanners — right, as he told TODAY earlier this year.)

The future is now, and it’s pretty cool. But what will the world be like in another 30 years? Three futurists shared their predictions with NBC News.

Katie Aquino, a.k.a. ‘Miss Metaverse’: Super-fast travel, nanomedicine and virtual immortality

“No longer will expensive and lengthy flights be the norm for world travel,” said the futurist and filmmaker known as Miss Metaverse. Instead, frictionless maglev trains will allow “us to travel at speeds in excess of 6,000 miles per hour while only feeling a G1 gravitational force, the same we feel when riding in a car.”

At those speeds, going from New York to Beijing will only take two hours. And if you get sick on your trip?

“Nanotechnology, although not a hot topic today, will likely unlock the keys to destroying cancer cells and ‘programming’ stem cells for a myriad of health benefits in the future,” she said.

Customized drugs will solve a lot of ailments. Death isn’t one of them, but we could still find a way to become immortal … kind of.

“Our future lives may truly be limitless thanks to an organization known as the 2045 Initiative that’s working towards a goal of uploading human consciousness into synthetic avatars,” she said. “Much like in the movie ‘Avatar,’ humans may evolve into what are theoretically known as post-humans, human consciousness in upgraded or synthetic bodies.”

Jamais Cascio: Jurassic pets and augmented reality clothing

Love the movie “Jurassic Park” but don’t like being eaten by terrifying symbols of man’s hubris?

Synthetic biology could let people create “miniature versions of various dinosaurs or other prehistorical creatures,” said writer and futurist Jamais Cascio. That might include a “mini-Velociraptor on a leash, with the right behavior modification to make sure it’s safe to be around,” or a “micro-Brontosaurus that’s perfect for a kid to ride.”

Of course, you want to look when riding around on your designer dinosaur. Hence the augmented reality clothing, which, Cascio said, will be visible to people wearing the “ubiquitous smart glasses, digital contact lenses, and eye upgrades.”

“Imagine a dress that looks like (and acts like) it’s made of water,” he said. “Or a Halloween costume that appears to be entirely made of living spiders.”

That would look great with a pair of sneakers with power laces.

James Canton: Digital memories and robot soldiers

Sharing a Facebook photo won’t seem very impressive in 2045, according to James Canton, a futurist, writer and business consultant.

That’s because people will share “entertainment memories,” which are “like real-time videos,” he said, “except others can experience the emotion, physical sensation and actual experience as if they were there.”

Intense and kind of creepy! Gene-editing will eliminate genetic diseases, he predicted, and replica organs will be printable on demand.

And yes, “Terminator” fans, there will be machine combat as “robots fight our wars, no more human soldiers.”

There is no guarantee that any of these technologies will arrive, of course. Hopefully by 2045, we will see at least some of the predictions from “Back to the Future Part II” come true, although there is a decent chance we still won’t have flying cars and the Chicago Cubs (currently losing in the playoffs to the Mets) will still be waiting for their first World Series win since 1908.

http://www.nbcnews.com/tech/innovation/beyond-back-future-experts-serve-tech-predictions-2045-n447311

Scientists Call for a Summit on Gene-Edited Babies

March 26, 2015

A group of senior American scientists and ethics experts is calling for debate on the gene-engineering of humans, warning that technology able to change the DNA of future generations is now “imminent.”

In policy recommendations published today in the journal Science, eighteen researchers, including two Nobel Prize winners, say scientists should accept a self-imposed moratorium on any attempt to create genetically altered children until the safety and medical reasons for such a step can be better understood.

The concern is over a rapidly advancing gene-editing technology, called CRISPR-Cas9, which is giving scientists the ability to easily alter the genome of living cells and animals (see “Genome Surgery”). The same technology could let scientists correct DNA letters in a human embryo or egg cell, for instance to create children free of certain disease-causing genes, or perhaps with improved genetics.

“What we are trying to do is to alert people to the fact that this is now easy,” says David Baltimore, a Nobel Prize winner and former president of Caltech, and an author of the letter. “We can’t use the cover we did previously, which is that it was so difficult that no one was going to do it.”

Many countries already ban “germ line” engineering—or changing genes in a way that would be heritable from one generation to the next—on ethical or safety grounds. Others, like the U.S., have strict regulations that would delay the creation of gene-edited children for years, if not decades. But some countries have weak rules, or none at all, and Baltimore said a reason scientists were speaking publicly now was to “keep people from doing anything crazy.”

The advent of CRISPR is raising social questions of a kind not confronted since the 1970s, when the ability to change DNA in microӧrganisms was first developed. In a now famous meeting in 1975, in Asilomar, California, researchers agreed to avoid certain kinds of experiments that were then deemed dangerous. Baltimore, who was one of the organizers of the Asilomar meeting, says the scientists behind the letter want to offer similar guidance for gene-engineered babies.

The prospect of genetically modified humans is surprisingly close at hand. A year ago, Chinese researchers created monkeys whose DNA was edited using CRISPR (see “10 Breakthrough Technologies 2014: Genome Editing”).

Since then, several teams of researchers in China, the U.S., and the U.K. have begun using CRISPR to change the DNA of human embryos, eggs, and sperm cells, with an eye toward applying the technology at in vitro fertility (IVF) clinics. That laboratory research was described by MIT Technology Review earlier this month (see “Engineering the Perfect Baby”).

Last week, in Nature, representatives of an industry group, the Alliance for Regenerative Medicine, recommended a wider moratorium that would also include a cessation of such laboratory studies, which it termed “dangerous and ethically unacceptable” (see “Industry Body Calls for Gene-Editing Moratorium”).

But that position was rejected by the authors of the current Science editorial. Instead, they said basic research on germ line engineering should move forward, including efforts to determine “what clinical applications, if any, might in the future be deemed permissible.”

Today’s statement was organized by Jennifer Doudna, a University of California, Berkeley, biologist who codiscovered the CRISPR technology. She confirmed that the group supports using it to edit the DNA of early-stage human embryos if it’s for scientific research.

That recommendation could come as a bombshell to critics of germ line engineering, as well as religious groups. Some believe an ethical “bright line” should separate humanity from the kind of gene-tinkering used on plants, microbes, and animals. If so, what is the point of testing the technology in human embryos?

But some authors of the Science editorial believe basic research must be given a free hand. “Science should not be impeded in its earliest stages by concerns that improvements in, and validations of, certain parts of the technology are opening the door to eugenics,” says Paul Berg, a professor emeritus at Stanford’s medical school, who also signed the letter. Berg said he supported research aimed at “perfecting the technology in preparation for the time when society could sanction germ line modification in medicine.”

A growing industry has already sprung up around gene editing, which is being applied to lab animals and farm species, and is being contemplated as a way to treat adults with diseases like muscular dystrophy or HIV infection. Such treatments of sick individuals are known as somatic gene therapy, and were not the subject of the current editorial, or the call for a moratorium.

Theoretically, germ line editing could correct genes that lead to lethal diseases before birth. For instance, if a person had Huntington’s disease, caused by a single faulty gene, CRISPR could be used to eliminate the mutation from that person’s children.

One biotechnology company, OvaScience of Cambridge, Massachusetts, has invested more than $2 million dollars investigating whether gene-editing could be used in IVF procedures. OvaScience did not respond to a request for comment.

While correcting inherited disease genes could prove medically useful, the authors of the Science editorial said much remained unknown. “Even this seemingly straightforward scenario raises serious concerns,” they said of editing disease genes back to their healthy form. That is because scientists are unable to predict all the consequences of changing DNA letters in a person, especially if multiple genes were corrected at once.

“You would be making changes in generations to come, in ways that are very hard to predict,” says Baltimore.

In their editorial, the researchers call for high-level technical forums to discuss CRISPR, as well as convening a “globally representative” group of government agencies, ethics experts, and scientists to recommend policies. In the meantime, they say, scientists must refrain from actually producing genetically engineered babies, even though the opportunity to do so now exists.

“Scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical applications in humans,” they write

 

http://www.technologyreview.com/news/536021/scientists-call-for-a-summit-on-gene-edited-babies/

 

 

Tool to edit DNA revolutionizing research in Boston area

December 3, 2014

                   George Church, a genetics professor at Harvard Madical School

It is a fascinating quirk of nature: Simple bacteria have an immune system with a memory, which allows them to destroy invading viruses they have encountered in the past.

The phenomenon is more than just a scientific curiosity. In just two years, scientists have discovered how to repurpose the simple virus-shredding technique used by bacteria in more complicated creatures, a feat that is now revolutionizing research across the Boston area and beyond.

Using the procedure, which allows them to slice the genome with great precision — to edit it, in effect — scientists can cut and paste DNA synthesized in the laboratory to create animal versions of human cancers or blood cells resistant to HIV.

Local researchers have founded two companies aimed at turning the technique into a therapy to fix errant genes that cause a range of illnesses. Meanwhile, almost every week the method seems to be used for a new purpose: MIT researchers have used it to rapidly engineer mice with liver tumors; Harvard researchers have used it to disrupt genes and lower cholesterol levels in mice; and Children’s Hospital Boston scientists have, using human stem cells, corrected gene mutations that cause a rare blood disorder.

“I’m a technology junkie — an early adopter of all kinds of technology, not just biology, and it’s very rare to see something like this,” said George Church, a professor of genetics at Harvard Medical School whose laboratory did early work showing the technique could be used to “edit” genes in human cells. “As soon as we started playing with it in the lab, it became evident that not only was it something that worked well and worked efficiently, it was super easy to do.”

The technique, called CRISPR — short for “clustered regularly interspaced short palindromic repeats” — was developed in 2012 by scientists in California and in Europe who already are considered shoo-ins for a Nobel Prize. But the rapid progress and wide adoption of the technology have depended critically on the work of local leaders, who have pushed the process forward by proving that it worked in cells of all types, ranging from zebrafish embryos to mouse and human cells.

<br />

The technique has become so ubiquitous that it has entered the casual vernacular of science as a verb; people talking about “CRISPRing” genes they want to tweak or delete.

“It was cool that the bacteria had invented a way for doing this a billion years ago, but it was not at all clear that would be something you could reengineer for the human genome and the mouse genome. There were a lot of reasons it might not work,” said Eric Lander, founding director of the Broad Institute in Cambridge. “It’s extraordinarily powerful as a research tool. Less than 24 months . . . from an idea that might or might not work, to an idea every graduate student knows about and it’s a routine thing.”

For several decades, biologists have known about spotsin the DNA of bacteria where short sequences repeat that seemed to serve no purpose. During the past decade, it became clear that this assemblage of genetic junk was actually useful, providing a simple way for bacteria to remember and slash an invading virus with molecular scissors.

Jennifer Doudna of the University of California Berkeley and Emmanuelle Charpentier, who now works at the Helmholtz Centre for Infection Research in Germany, worked to show the technology could be customized to snip DNA strands at specific spots in a laboratory dish.

“When I first saw that paper, my thought was: If this works, it will really change the game again,” said Dr. J. Keith Joung, associate chief of pathology for research at Massachusetts General Hospital. The question he and others had was whether it would work outside of bacteria.

Within months, Church and Feng Zhang at the Broad Institute had begun to show the power of the technique, using it to cut genes in mouse and human cells. Joung showed that it could work in a living organism,engineering the genomes of zebrafish embryos.

A Cambridge-based company, Editas Medicine, was founded to work toward developing a therapy based on gene-editing. Local scientists also helped found a company called CRISPR Therapeutics with similar aims.

Meanwhile, academic scientists in a wide range of fields have adopted the simple-to-use technique, each using it in service of their own interests.

Cancer researchers, for example, have found that the tool can be used to rapidly create animals with multiple mutations that drive cancers, which might have taken months or years to engineer using older techniques.

“The method is so powerful that virtually every project in my lab is now using this technique,” said Tyler Jacks, director of the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology.

At the Harvard Stem Cell Institute, scientists working on blood stem cells showed earlier this month that it was possible to edit blood-forming stem cells. They were able to delete a gene called CCR5 that the HIV virus needs to infect blood cells.

Derrick Rossi, an associate professor of stem cell and regenerative biology at Harvard who co-led the blood stem cell work, said that previous gene-editing techniques had not seemed versatile or efficient enough to have significant potential for human patients.

“Data with those technologies never suggested to me it was going to be able to reach the type of efficacy that would be clinically translatable, and that’s actually why I got so excited and that’s what drew me to CRISPR,” Rossi said.

Daniel Anderson,a professor of applied biology at MIT’s Koch Institute, showed earlier this year that CRISPR could be used to correct a genetic liver disease in a mouse. That is an early demonstration of CRISPR’s potential to treat diseases caused by genetic mutations.

“Lots of things like that weren’t possible before now are doable,” said Craig Mello, a UMass Medical School biologist and Nobel laureate. Mello sees the technology’s power to transform medicine and to solve some of science’s most enduring mysteries.

“It’s still a huge mystery how we work and just basic biology,” Mello said. “We’re just trying to figure out this amazingly complicated and sophisticated mechanism we call life.”

 

http://www.bostonglobe.com/metro/2014/11/30/tool-easily-edit-dna-transforms-research-holds-potential-for-medicine/X7srGGFardarsWBfCqEL2H/story.html